The vascular smooth muscle cells (VSMC) are the predominant cell in the vascular wall. With injury to the vessel wall (e.g. atherosclerosis and after balloon angioplasty), the local release of growth factors (e.g. PDGF) and cytokines (e.g. gamma-IFN) acts as a stimulus for smooth muscle cells to produce protein products, to migrate and to proliferate. Transcriptional pathways, shared by gamma-IFN and PDGF and other cytokines and factors involved in the vascular response to injury or atherosclerosis, include members of the STAT family (signal transducer and activator of transcription) of transcription factors. STAT proteins become tyrosine phosphorylated directly or through JAK family kinases by plasma membrane receptors, translocates to the nucleus, and binds specific DNA sequences in gene promoter regions. We found that after balloon injury to the rat carotid artery, a neointima is formed that stained significantly for gamma-IFN. There was no evidence of T cells or macrophages/monocytes in these lesions. In atherosclerostic lesions, there are numerous activated T cells secreting gamma-IFN. Previously, we found that gamma-IFN increased the expression of STAT1 in cultured vascular smooth muscle cells and, therefore, we propose that gamma-IFN present within these vascular lesions likewise increased STAT1 protein expression. A combination of increased STAT expression and activation may lead to a different program of gene activation by the smooth muscle cells. In these studies, carotid arteries from control and injured (balloon angioplasty) rats were sectioned for immunostaining or protein extracted for Western blotting of STAT proteins. We found that after balloon injury (5 to 56 days), there is an increase expression of STAT1 and STAT3 proteins throughout the wall of the vessel but primarily in neointimal and advential cells. STAT1 and STAT3 staining was most prominent in the neointimal cells surrounding the lumen of the vessel and coincided with areas of more intense IFN-gamma staining. STAT5 and 6 staining also increased in cells throughout the neointima, but did not correspond with gamma-IFN staining. Western blots of protein extracts from carotid arteries confirmed the increase in STAT protein expression. From these studies we conclude that after injury to the carotid artery, the expression of STAT proteins increases, especially in the neointima. Changes in the expression of this family of transcription factors may contribute to the development of a neointima in this model of vascular injury, since STAT proteins represent a common signaling pathway for factors as diverse as platelet-derived growth factor, angiotensin II, and g-IFN involved in the vascular response to injury.